This application is a competitive renewal of a project directed at furthering the understanding of the basic scattering mechanisms of ultrasound in biological tissues, particularly in blood. The aims for the next grant period remain unchanged. (1) The applicants propose to continue the investigation of ultrasonic scattering properties of whole blood and erthyrocyte suspensions under well-defined flow conditions under steady and pulsatile flow either in an in vitro mock flow loop or in vivo on pigs. An emphasis will be placed on investigating the effect of vessel wall compliance on the cyclic variation of ultrasonic backscatter from whole blood. (2) The applicants propose to extend both the in vitro scattering measurements on blood and other soft tissues including myocardium, liver, and kidney to 60 MHz or higher using a modified substitution method. (3) The applicants propose to also explore the feasibility of using the acquired knowledge for developing new non-invasive methods for measuring fetal hematocrit and diagnosing vascular diseases. The rationale for pursuing Tasks 1 and 2 is that this knowledge is needed for the better interpretation of ultrasonic B-mode images and the further development of new methods for imaging blood flow. There has been an urgent need in this information because of the emerging clinical applications of intravascular ultrasonic imaging which typically is operated at frequencies higher than 20 MHz, Doppler power mode imaging, and non-Doppler blood flow imaging. In the first application, it has been shown that frequencies approaching 40 MHz have to used in order to be clearly visualize structures in the blood vessel wall. In the latter applications, Doppler power and echo amplitude are used to produce a color map to indicate tissue perfusion or blood supply. Clinical applications of these techniques depend upon a clear understanding of the relationship between Doppler power and echo amplitude from blood and hematological and hemodynamic parameters. Another rationale for pursing Tasks #2 is that although the next frontier of ultrasonic imaging appears to be in very high frequency (VHF) imaging in the range of 30 to 80 MHz, data on attenuation and scattering properties of soft tissues in this frequency range are lacking apparently due to experiment difficulties including the unavailability of sensitive high frequency transducers and suitable methodology. The rationale for pursuing Task #3 is that the magnitude of the cyclic variation of whole blood under pulsatile flow and the relationship between the cyclic variation and the flow waveform have been shown to be related to the hematocrit and vessel wall compliance. A better understanding of these relationships may lead to methods that can be used to estimate these parameters non-invasively.